The biological significance of double-stranded RNA (dsRNA) is reflected in the increasing evidence which indicates that dsRNA exerts a regulatory effect on a broad spectrum of biological systems. Specific effects include: (a) the induction of interferon; (b) cytotoxic effects on cells; (c) suppression of tumor development; (d) enhancement of the immune response; and (e) inhibition of protein synthesis. Several striking features common to these physiological mechanisms are (1) the lack of specificity of the dsRNA inducer, (2) sensitivity of physiological levels of dsRNA, and (3) the capacity of viral replicative intermediates to replace pure dsRNA. The broad objective of our research effort has been to determine the molecular basis for these effects, with particular emphasis on the control of protein synthesis by dsRNA, an ubiquitous feature of those biological systems. The reticulocyte lysate is particularly responsive to dsRNA and has provided us with a laboratory model for the study of several biological mechanisms induced by dsRNA similar to those observed in interferon-sensitized cells, including (1) the activation of a protein kinase which regulates protein synthesis; and (2) the activation of a (2'-5') oligo A synthetase whose product promotes nuclease activity. A primary conclusion of our studies and others as well is the importance of phosphorylation-dephosphorylation events in the regulation of translation and transcription. Projected research efforts based on these findings will focus on two areas: (1) Studies on the control of translation will deal with the nature and function of the dsRNA-induced protein kinase in interferon-treated cells including HeLa, human diploid fibroblasts, Krebs ascites, as well as induced Friend erythroleukemia cells. (2) A study on the control of transcription by phosphorylation will be initiated using isolated nuclei of induced and uninduced Friend cells.